By Randall Osborne

After delaying its Phase III trial to file paperwork with the FDA detailing the company's manufacturing plan, Avax Technologies Inc. said the agency has cleared it to conduct the enlarged study of M-Vax, an autologous vaccine for stage 3 melanoma.

"We've done all the business of the trial," said Jeffrey Jonas, president and CEO of Kansas City, Mo.-based Avax. "We're still projecting the same timeline we projected in October."

Jonas said the company "could conceivably file [a new drug application] in a year," based on data from the trial, but filing in late 2000 or 2001 is more likely.

In October Avax said it began a Phase III trial with 250 subjects. The company halted enrollment when the FDA asked for manufacturing data, and the new study will include 400 patients. (See BioWorld Today, Oct. 31, 1997, p. 1.)

"There are no functional autologous therapies that have gone into large-scale trials," Jonas said. Genzyme Corp., of Cambridge, Mass., markets Carticel, which uses autologous cultured chondrocytes to repair cartilage on the thigh bone part of the knee, but that product is considered "structural," he added.

The randomized study of M-Vax at about 25 sites will test the vaccine as postsurgical adjuvant therapy, comparing its efficacy against high dosages of alpha interferon. Its two endpoints are rate of tumor recurrence and overall survival rate.

"The primary endpoint is disease-free survival," Jonas said.

A Phase II trial showed two-thirds of patients who had six weeks of therapy with M-Vax developed an immune response against their own tumor cells as measured by a standard skin test. The Phase III study will use an identical protocol.

Other studies have verified the positive response, which was correlated with overall survival benefit for those treated with the vaccine.

An autologous cell vaccine works by conjugating the patient's tumor cells to a small molecule known as a hapten (dinitro phenyl), then injecting them back into the patient along with an agent that boosts immune response (cyclophosphamide, commonly used in chemotherapy).

"Haptenized" molecules sometimes elicit an immune response against the unmodified cancer molecule as well.

"Cells from the tumor are separated into a suspension, put out into doses and frozen until the patient requires them," Jonas said. "If the patient wants to have chemotherapy first, or take a break from therapy, we can hold the cells."

The cells, kept in a central location, may be stored for about a year and shipped as needed. Processing the vaccine on demand takes two to three hours.

"We have a minimum of 18 hours' stability on the way out, and we're looking to validate more," Jonas said.

"Most people will tell you autologous therapy has efficacy, but the challenge has been thinking of a way to make it commercially viable," he added. Jonas said Avax has found a way, using its "just-in-time" shipping.

Filing another investigational new drug application "complete with manufacturing details" after last year's holdup will allow Avax to begin manufacturing shortly after approval.

"From the company's standpoint, we suffered a delay to answer a lot of questions, but we think that's the right way to do it," Jonas said.

Avax's stock (NASDAQ:AVXT) closed Monday at $2.125, down $0.156. *